The focus of this proposal is to define the relationship between the Toll signal transduction pathway and the innate immune response of the zebrafish. By examining the way in which the Toll pathway responds to infectious diseases, and by developing a deeper understanding of how this facet of innate immunity regulates adaptive immunity, we seek to find ways to augment, extend, and prolong the immune response. We will conduct functional analysis of the Toll pathway and develop reagents that will be essential tools for other researchers in this field. The SPECIFIC AIMS of this proposal are to: 1. Determine the extent to which the Toll signaling pathway is linked to the activation of the innate immune response. Evaluate the role of the Toll pathway in response to infection using NF-kappaB indicator transgenic fish By examining the Toll signaling pathway in the zebrafish and determining its role in protective immunity against pathogens, we will gain a more complete understanding of the impact of innate immunity on the function and development of the immune system, and how this pathway has contributed to the evolution of the modern adaptive immune response.